Professor of Clinical Pharmacy
There are more than 130 different therapeutic proteins or peptides that are used to treat a broad range of illnesses. One of these proteins, tissue plasminogen activator (tPA), has been used to treat myocardial infarction and stroke. Dr. Stringer's laboratory has determined that in addition to its proteolytic function, tPA has anti-inflammatory activity. The combination of these two properties could make tPA a viable therapeutic approach to treat inflammatory-fibrotic lung diseases such as acute respiratory distress syndrome (ARDS) and idiopathic pulmonary fibrosis (IPF) and the rare, most often pediatric disease, plastic bronchitis (PB). To this end, the Stringer laboratory has developed a formulation of tPA (pf-tPA) for targeted pulmonary delivery and is focused on three main areas of research:
Pulmonary Delivery of Therapeutic Proteins
Candidate therapeutic proteins are formulated for pulmonary delivery using a range of assays to assess protein stability. Aerodynamic particle size and biological function following nebulization are measured to ensure the feasible of candidate formulations. Respiratory deposition is also characterized in experimental models of pulmonary dosing and of acute lung injury in order to gather pharmacodynamic, pharmacokinetic and toxicological as well as therapeutic response data. Collectively, this line of investigation enables the Stringer laboratory to test the feasibility of local pulmonary delivery of therapeutic proteins in man.
Pathogenesis of Inflammatory-Fibrin Lung Diseases
Pulmonary illnesses such as acute lung injury (ALI)/ARDS, IPF and PB remain clinically challenging problems for a number of reasons including poorly understood complex physiology and patient heterogeneity. The absence of biomarkers that predict disease onset, progression and severity have had a negative impact on our ability to identify and develop effective pharmacotherapy aimed at improving morbidity and mortality in patients with critical illness. The Stringer research group is utilizing a broad systems biology approach that encompasses metabolomics, transcriptomics, and genomics with the powerful tool of computational analysis. The work is aimed at identifying the metabolic signatures of ALI and PB.
Mechanisms and Disposition of Therapeutic Proteins in Inflammatory Lung Disease
Inflammatory lung disease is a significant risk to human health. Presently, the Stringer lab is focused on optimizing the use of pf-tPA for the treatment of PB. We are optimizing dosing strategies using ex vivo approaches that utilize cast from patients with PB. In addition, the lab is developing an animal model of PB that encompasses elements of derangement of the fibrinolytic and inflammatory systems so that a more accurate assessment of pf-tPA efficacy and safety in the treatment of PB can be made.